We propose to search for antitumor agents in the plant tribe Senecioneae and especially in the large genus Senecio, which is known to be rich in pyrrolizidine alkaloids and eremophilane sesquiterpenoids. Semisynthetic means will be used to prepare more active agents on the basis of structure-activity studies. Thus, the necine base of the alkaloid will be derived from natural sources, while synthetic necic acids will be reattached to the bases. A similar approach is visualized in the furanoeremophilane sesquiterpenoids and related lactones. Antitumor screening will be done on extracts, fractions and pure compounds by the National Cancer Institute. Extractions and fractionations will be done according to the National Cancer Institute's recommended procedure, with separations accomplished by high performance liquid chromatography. Structure elucidation will depend whenever possible on X-ray analysis with routine use of 1H and 13C NMR and high resolution mass spectrometry.